Traditional hemostatic materials, such as gelatin sponges, microcrystalline collagens and collagen proteins, are prepared from skins and bones of animals, which easily result in antigen reaction of tissues. Additionally, these materials have large stimulation to the tissues, and after an operation, cicatricle tissues proliferate and adhesion easily occurs. Meanwhile, the materials are poor in stability and inconvenient in storage and use. The use of animal medical materials is thus restricted in the world. Natural vegetable hemostatic materials are being used to replace animal hemostatic materials.
Recently, reports and patents that relate to the use of oxidized cellulose, cellulose esters and ethers products as medically hemostatic materials have been found, however, most of the materials are water-insoluble.
U.S. Pat. No. 2,914,444 entitled with Cellulose hemostatic composition discloses a series of cellulose derivatives useful for hemostatic agents alone or in combination with each other, including cellulose sulfonic acid ester (substituting degree 1-3) or metal(sodium, potassium, calcium, magnesium, aluminum) salts thereof, cellulose glycolic acid ether (substituting degree 0.5-3.0) or metal salts thereof. U.S. Pat. No. 2,914,444 emphasizes that the product can be used only after being made water-insoluble. U.S. Pat. No. 3,122,479 entitled with Hemostatic surgical dressings discloses methods for making the materials of the above-mentioned invention into water-insoluble sponges, slightly water-soluble elastic films and water-insoluble oxidized cellulose compressed cottons. U.S. Pat. No. 2,764,159 entitled with Absorbable products discloses a method for making absorbable fiber filaments, sponges, films and powders comprising dissolving a cellulose glycolic acid ether salt, spinning, and then making it into an insoluble acid product by using an inorganic acid. According to U.S. Pat. No. 2,764,159, the free acid cellulose ethers have a viscosity less than 17.4 seconds in a 0.5N NaOH aqueous solution, preferably, 5.7-12.0 seconds; and a degree of substitution of 0.5-0.7, and at most 2.0. Soluble cellulose ether salts are used as starting materials in the first step for preparing the product; even though the final product contains a part of salt groups, it meantime must contain a certain proportion of free carboxylic acid groups, i.e., about 50% carboxylic acid groups remain un-neutralized, with a pH value of 2-5.5 to ensure the product insoluble or slightly soluble. Chinese patent application No. 97117113 entitled with Bio-absorbable medical materials from oxidized polysaccharides discloses the preparation of absorbable medical materials by using (methyl, ethyl, or carboxymethyl) cellulose ethers and other polysaccharides as starting materials and carrying out post-oxidation treatment. After being oxidized, except that methylcellulose ether is still soluble, other ethers products all become insoluble. Moreover, the cellulose derivatives of the patent application are used to prevent operation adhesion, and their hemostatic activity is not mentioned therein.
Chinese patent No. 1035803C describes a method for manufacturing water-soluble hemostatic fabrics. The method does not control the degree of substitution and the degree of polymerization of the product. However, the present applicant has found that the degree of substitution and the degree of polymerization of a product has a direct effect on its hemostatic effect. The patent states that the product of formula II can be absorbed in vivo, whereas the degree of polymerization of the product is disclosed as 800-1,200 (twice of 400-600). Thus the product will have a molecular weight greater than 120,000 and it will be difficult for the product to enter into circulating system via vascellum wall for excretion (See, S. D. Bruck, Properties of Biomaterial in the Physiological Environment, and D. F. Williams, Fundamental Aspects of Biocompatibility). In addition, as described hereinafter, the material having a too large degree of polymerization forms gel after being implanted in the body, has a large swelling volume, and produces oppression to peripheral tissues, which will cause inflammatory reaction, fiber proliferation, and formation of liquefied cavity.